异氟醚对缺锌APP/PS1转基因阿尔茨海默病模型小鼠海马神经元凋亡的影响

doi:10.13481/j.1671-587x.20180105

吉林大学学报(医学版) ›› 2018, Vol. 44 ›› Issue (01): 24-29.doi: 10.13481/j.1671-587x.20180105

异氟醚对缺锌APP/PS1转基因阿尔茨海默病模型小鼠海马神经元凋亡的影响

冯安琪¹, 刘楠¹, 朴美花¹, 苑野¹, 裴爱月², 刘娅³, 冯春生¹

1. 吉林大学第一医院麻醉科, 吉林长春 130021;
2. 吉林大学第一医院内镜中心, 吉林长春 130021;
3. 吉林大学公共卫生学院营养与食品卫生学教研室, 吉林长春 130021

收稿日期:2017-06-13 出版日期:2018-01-28 发布日期:2018-01-24
通讯作者: 冯春生,教授,硕士研究生导师(Tel:0431-88782955,E-mail:fcs1971@hotmail.com) E-mail:fcs1971@hotmail.com
作者简介:冯安琪(1992-),女,山西省长治市人,在读医学硕士,主要从事临床麻醉药物对于阿尔兹海默病发病机制影响方面的研究。
基金资助:
国家自然科学基金资助课题（81141065，81271215）；吉林省科技厅科技发展计划项目资助课题（20150101170JC）；中国博士后科学基金资助课题（2016M591489）

Effect of isoflurane anesthesia on hippocampus neuroapoptosis in zinc-deficient APP/PS1 transgenic mice of Alzheimer's disease models

FENG Anqi¹, LIU Nan¹, PIAO Meihua¹, YUAN Ye¹, PEI Aiyue², LIU Ya³, FENG Chunsheng¹

1. Department of Anesthesiology, First Hospital, Jilin University, Changchun 130021, China;
2. Department of Endoscope Center, First Hospital, Jilin University, Changchun 130021, China;
3. Department of Nutrition and Food Hygiene, school of Public Health, Jilin University, Changchun 130021, China

Received:2017-06-13 Online:2018-01-28 Published:2018-01-24

摘要/Abstract

摘要： 目的：研究吸入麻醉药异氟醚对缺锌APP/PS1转基因小鼠海马神经元凋亡的影响，探讨其相关作用机制。方法：8和9月龄APP/PS1转基因小鼠随机分为常锌组、常锌+异氟醚组、缺锌组和缺锌+异氟醚组，每组24只。常锌组小鼠给予正常锌含量饮食2个月；常锌+异氟醚组小鼠给予正常锌含量饮食2个月后接受1.4%异氟醚麻醉2 h；缺锌组小鼠给予低锌饮食1个月；缺锌+异氟醚组小鼠给予低锌饮食1个月后接受1.4%异氟醚麻醉2 h。分别在麻醉后6和24 h杀鼠取海马组织，采用免疫荧光双染法检测海马神经元凋亡率，Western blotting法检测海马β淀粉样蛋白（Aβ）、活化型半胱氨酸天门冬氨酸特异性蛋白酶3（Cleaved caspase-3）表达水平和Bax/Bcl-2比值。结果：与常锌组比较，常锌+异氟醚组小鼠麻醉后6 h海马神经元凋亡率、Cleaved caspase-3表达水平和Bax/Bcl-2比值升高（P<0.05或P<0.01），麻醉后24 h海马神经元凋亡率总Aβ、Aβ40和Aβ42表达水平无明显改变（P>0.05）；缺锌组和缺锌+异氟醚组小鼠麻醉后6和24 h海马神经元凋亡率、Aβ42表达水平、Cleaved caspase-3表达水平和Bax/Bcl-2比值升高（P<0.05或P<0.01）。与缺锌组比较，缺锌+异氟醚组小鼠麻醉后6和24 h海马神经元凋亡率、Aβ42和Cleaved caspase-3表达水平及Bax/Bcl-2比值进一步升高（P<0.05或P<0.01）。结论：10月龄常锌APP/PS1转基因小鼠给予1.4%异氟醚麻醉2 h能够短暂加重其海马神经元凋亡；1.4%异氟醚麻醉2 h能够明显加重缺锌APP/PS1转基因小鼠海马神经元凋亡，其作用机制可能与促进海马Aβ42聚集、增强Bax表达、抑制Bcl-2表达和激活Caspase-3有关。

关键词: 神经元凋亡, 阿尔茨海默病, 缺锌, 异氟醚, β淀粉样蛋白

Abstract: Objective: To study the effect of isoflurane anesthesia on the hippocampal neuroapoptosis in the zinc-deficient APP/PS1 transgenic mice,and to clarify its related mechanisms. Methods: The eight-month or nine-month old APP/PS1 transgenic mice were randomly assigned to four groups (n=24):zinc adequate(ZA) group,the mice were given a standard diet for 2 months; zinc adequate+ isoflurane(ZA+Iso) group,the mice were given a standard diet for 2 months then exposed to 1.4% isoflurane for 2 h; zinc-deficient(ZD) group,the mice were given zinc deficient diet for 1 month; zinc deficient with isoflurane(ZD+Iso)group,the mice were given zinc deficient diet for 1 month and then exposed to 1.4% isoflurane for 2 h. The hippocampus tissue of the mice were obtained 24 h after anesthesia. The immunofluorescence double staining was performed to measure the apoptotic rates of hippocampal neurons. The Western blotting method was used to detect the expression levels of Aβ and Cleaved caspase-3 and the ratio of Bax/Bcl-2. Results: Compared with ZA group,the apoptotic rate of neurons,the ratio of Bax/Bcl-2 and the expression level of Cleaved caspase-3 of the mice in ZA+Iso group were increased 6 h after isoflurane exposure(P<0.05 or P<0.01);but no differences were found in the apoptotic rate of neurons and the expression levels of total Aβ,Aβ40 and Aβ42 24 h after isoflurane exposure(P>0.05).Compared with ZA group,the apoptotic rates of neurons,the ratios of Bax/Bcl-2,the expression levels of Aβ42 and Cleaved caspase-3 of the mice in ZD group and ZD+Iso group were increased 6 and 24 h after isoflurane exposure(P<0.05 or P<0.01).Compared with ZD group,the apoptotic rate of neurons,the expression levels of Aβ42,Bax/Bcl-2 and Cleaved caspase-3 and the ratio of Bax/Bcl-2 of the mice in ZD+Iso group were elevated significantly 6 and 24 h after isoflurane exposure(P<0.05 or P<0.01). Conclusion: 1.4% isoflurane exposure for 2 h can induce the transient elevation of hippocampal neuroapoptosis in the ten-month old APP/PS1 transgenic mice.1.4% isoflurane exposure for 2 h can significantly aggravate the hippocampal neuroapoptosis in the zinc-deficient APP/PS1 transgenic mice,it is probably associated with the hippocampal Aβ aggregation,activation of Bax and Caspase-3 and inhibition of Bcl-2.

Key words: zinc deficiency, neuron apoptosis, Alzheimer's disease, amyloid β-peptide, isoflurane

中图分类号:

R743

冯安琪, 刘楠, 朴美花, 苑野, 裴爱月, 刘娅, 冯春生. 异氟醚对缺锌APP/PS1转基因阿尔茨海默病模型小鼠海马神经元凋亡的影响[J]. 吉林大学学报(医学版), 2018, 44(01): 24-29.

FENG Anqi, LIU Nan, PIAO Meihua, YUAN Ye, PEI Aiyue, LIU Ya, FENG Chunsheng. Effect of isoflurane anesthesia on hippocampus neuroapoptosis in zinc-deficient APP/PS1 transgenic mice of Alzheimer's disease models[J]. Journal of Jilin University Medicine Edition, 2018, 44(01): 24-29.

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异氟醚对缺锌APP/PS1转基因阿尔茨海默病模型小鼠海马神经元凋亡的影响

Effect of isoflurane anesthesia on hippocampus neuroapoptosis in zinc-deficient APP/PS1 transgenic mice of Alzheimer's disease models

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